Nitric oxide (NO) is an important mediator in biological systems, playing significant roles in physiology and pathophysiology. For instance, cellular responses to NO are often transduced via multiple chemical reactions, including direct reactions with heme centers and metalloproteins, as well as indirect reactions, including oxidative and other metabolic reactions with various reactive nitrogen species. In particular, reactions of certain reactive nitrogen species with cysteine thiols on proteins that result in nitrosylation of the protein may represent an important post-translational modification capable of transducing certain NO-dependent signals.
Many proteins have been characterized as being targets for S-nitrosylation reactions, including metabolic proteins, structural proteins, cytoskeletal proteins, ion channels, and signaling proteins. In many cases, S-nitrosylation is believed to regulate protein activity and function. For example, S-nitrosylation has been shown to inhibit the activity of caspases, and denitrosylation is often required for the enzymatic activity of these enzymes. Similarly, the S-nitrosylation of p50, which is a subunit of transcription effector nuclear factor kappa B (NF-κB), is believed to be responsible for the NO-induced inhibition of DNA binding activity of transcription factor NF-κB.
Many of the proteins targeted by S-nitrosylation were originally identified using exogenous NO donors, and it has not always been established whether S-nitrosylation of these proteins is associated with endogenous NO activity. This is primarily due to limitations in the methodology typically used to detect S-nitrosylated proteins.